Kerr microresonator dual-comb source with adjustable line-spacing.

Optical microresonators offer a highly-attractive new platform for the generation of optical frequency combs. Recently, several groups have been able to demonstrate the generation of dual-frequency combs in a single microresonator driven by two optical pumps. This opens the possibility for microresonator-based dual-comb systems suitable for measurement applications such as spectroscopy, ranging and imaging. Key to the performance of these systems are the parameters of the radio-frequency comb spectrum that arises from the interference of the two optical combs. In this work, we present a simple mechanism to enable the discrete fine-tuning of these parameters by driving the two optical combs with optical pumps with different azimuthal mode numbers. The mechanism consists of tuning the difference in azimuthal mode number between the two pumps by selection of the pumps' frequencies. We are able to implement this technique when the two counter-propagating pumps are set to drive resonances of the same spatial mode family, as well as different mode families. In each case, we experimentally observe ∼1 MHz of discrete tunability in the line-spacing of the radio-frequency comb as the frequency offset between the two pumps is scanned between 0 to 80 free-spectral-ranges.

Exercise therapy guides cortical reorganization after midthoracic spinal contusion to enhance control of lower thoracic muscles, supporting functional recovery.

Postural control is critical for locomotion, allowing for gait changes, obstacle avoidance and navigation of rough terrain. A major problem after spinal cord injury (SCI) is regaining the control of balance to prevent falls and further injury. While the circuits for locomotor pattern generation reside in the spinal cord, postural control consists of multiple, complex networks that interact at the spinal, brainstem and cortical levels. After complete SCI, cortical reorganization establishes novel control of trunk musculature that is required for weight-supported stepping. In this study, we examined the impact of exercise therapy on cortical reorganization in the more clinically relevant models of both moderate and severe midthoracic contusion injury in the rat. Results demonstrate that both spontaneous recovery and therapy induced recovery of weight-supported stepping utilize cortical reorganization. Moreover, exercise therapy further improves outcome by enhancing cortical control of lower thoracic muscles enabling improvements in interlimb coordination associated with improved balance that increases weight-supported stepping. The outcome of this study suggest that cortical control of posture is key to functional improvement in locomotion. This information can be used to improve the timing and type of therapy after SCI by considering changes along the entire neural axis.

Pharmacokinetics of bleomycin sclerotherapy in patients with vascular malformations.

Bleomycin, a chemotherapy agent that inhibits synthesis of DNA, has been increasingly utilized in sclerotherapy for patients with vascular malformations. A serious long-term risk of intravenous bleomycin is dose-dependent interstitial pneumonitis. Little is known about absorption and circulating levels of bleomycin when used in sclerotherapy for patients with vascular malformations. This is an Institutional Review Board (IRB)-approved prospective study on patients receiving bleomycin sclerotherapy in the management of vascular malformations. Depending on the type of vascular malformation, bleomycin was administered either in the lumen or interstitial space of the involved lesion. A bleomycin assay measured serum bleomycin plasma concentrations versus time at seven intervals following treatment. Pharmacokinetic parameters were obtained for each participant and included peak plasma concentration (Cmax ), time to reach peak plasma concentration (Tmax ), volume of distribution (Vd ), elimination half-life (t1/2 ), the volume of plasma cleared of the drug per unit time (CL), and total systemic exposure area under the curve (AUC). Fifteen patients were enrolled (5: lymphatic, 4: venous, 6: arteriovenous malformations). Bleomycin was administered interstitially (IS) in 11 patients and intraluminal (IL) in four; median age of 13 years (range: 2-67). Pharmacokinetic analysis revealed terminal elimination half-life (t1/2λz ) of 88.51 (±23.09) and 111.61 (±37.75) minutes for the IS and IL groups, respectively. Vd was 4.86 L (±6.74) and 1.55 L (±0.54) for the IS and IL groups, respectively. AUC was 53.9 (±23.45) and 129.17 (±93.57) mg min/L for the IS and IL groups, respectively. There were no statistically significant differences in t1/2λz , Vd , or AUC parameters between groups. Bleomycin is absorbed systemically when used as a sclerosant for vascular malformations when injected either IS or IL.

Analyzing coagulation dynamics during treatment of vascular malformations with thromboelastography.

BACKGROUND/OBJECTIVES: Slow-flow vascular malformations are abnormal vessels that can lead to activation and consumption of coagulation factors and thrombosis, known as localized intravascular coagulopathy (LIC). Most clinical and research evidence of vascular malformation hemostasis relies on conventional coagulation studies, which may not provide a complete picture. Thromboelastograpy (TEG) is a tool that can provide real-time assessment of a patient's coagulation dynamics, and may allow for a more individualized treatment approach. We hypothesized that patients with slow-flow vascular malformations will have changes in TEG parameters peri-procedure that will help predict blood product or medication administration. DESIGN/METHODS: Institutional Review Board approved prospective study of patients with slow-flow vascular malformations undergoing a sedated, minor procedure. TEG and conventional coagulation studies were obtained preprocedure, 15 min, and when possible, at 30 min after the start of the procedure. RESULTS: Twenty-five patients were enrolled. Median age was 15 years (range 3-47 years). Procedures included laser and/or sclerotherapy. There were no changes in TEG parameters from baseline to 15 min or 30 min. The following decreased from baseline to 15 min: fibrinogen 313 to 287 mg/dL (P = .001), D-dimer 1.3 to 1.1 mg/L (P = .02), hemoglobin 12.8 to 11.8 g/dL (P = .001), and platelet count 272 000 to 256 000 (P = .006). No patient had a bleeding/thrombotic complication during or within 1 week postprocedure. CONCLUSION: We saw no change in TEG parameters or bleeding or clotting complications despite significant numerical changes in conventional coagulation profiles, suggesting that conventional studies may not be as useful in determining risks of bleeding or thrombotic complications peri-procedure for minor procedures.

Mineralocorticoid receptor antagonism by finerenone is sufficient to improve function in preclinical muscular dystrophy.

AIMS: Duchenne muscular dystrophy (DMD) is an X-linked inherited disease due to dystrophin deficiency causing skeletal and cardiac muscle dysfunction. Affected patients lose ambulation by age 12 and usually die in the second to third decades of life from cardiac and respiratory failure. Symptomatic treatment includes the use of anti-inflammatory corticosteroids, which are associated with side effects including weight gain, osteoporosis, and increased risk of cardiovascular disease. Novel treatment options include blockade of the renin-angiotensin-aldosterone system, because angiotensin as well as aldosterone contribute to persistent inflammation and fibrosis, and aldosterone blockade represents an efficacious anti-fibrotic approach in cardiac failure. Recent preclinical findings enabled successful clinical testing of a combination of steroidal mineralocorticoid receptor antagonists (MRAs) and angiotensin converting enzyme inhibitors in DMD boys. The efficacy of MRAs alone on dystrophic skeletal muscle and heart has not been investigated. Here, we tested efficacy of the novel non-steroidal MRA finerenone as a monotherapy in a preclinical DMD model. METHODS AND RESULTS: The dystrophin-deficient, utrophin haploinsufficient mouse model of DMD was treated with finerenone and compared with untreated dystrophic and wild-type controls. Grip strength, electrocardiography, cardiac magnetic resonance imaging, muscle force measurements, histological quantification, and gene expression studies were performed. Finerenone treatment alone resulted in significant improvements in clinically relevant functional parameters in both skeletal muscle and heart. Normalized grip strength in rested dystrophic mice treated with finerenone (40.3 ± 1.0 mN/g) was significantly higher (P = 0.0182) compared with untreated dystrophic mice (35.2 ± 1.5 mN/g). Fatigued finerenone-treated dystrophic mice showed an even greater relative improvement (P = 0.0003) in normalized grip strength (37.5 ± 1.1 mN/g) compared with untreated mice (29.7 ± 1.1 mN/g). Finerenone treatment also led to significantly lower (P = 0.0075) susceptibility to limb muscle damage characteristic of DMD measured during a contraction-induced injury protocol. Normalized limb muscle force after five lengthening contractions resulted in retention of 71 ± 7% of baseline force in finerenone-treated compared with only 51 ± 4% in untreated dystrophic mice. Finerenone treatment also prevented significant reductions in myocardial strain rate (P = 0.0409), the earliest sign of DMD cardiomyopathy. Moreover, treatment with finerenone led to very specific cardiac gene expression changes in clock genes that might modify cardiac pathophysiology in this DMD model. CONCLUSIONS: Finerenone administered as a monotherapy is disease modifying for both skeletal muscle and heart in a preclinical DMD model. These findings support further evaluation of finerenone in DMD clinical trials.

A retrospective review to identify criteria for incorporating the Singapore flap and gracilis muscle flap into obstetric fistula repair.

OBJECTIVE: To identify criteria to guide surgeons regarding indications for use of the Singapore and gracilis muscle flaps in obstetric fistula repair. METHODS: This is a retrospective case series. Obstetric fistula surgeons in Lilongwe, Malawi, have been incorporating plastic surgery techniques with the Singapore and gracilis muscle flaps since collaborating with plastic surgeons in 2016. We describe the surgical outcomes of procedures utilizing each flap individually and those using both. RESULTS: Between February 2016 and June 2019, 69 patients received a flap at the time of obstetric fistula repair at the Fistula Care Center in Lilongwe, Malawi. A total of 32 (46.4%) received a Singapore flap, 20 (29.0%) received a gracilis flap, and 17 (24.6%) received both types of flap. CONCLUSION: Based on our outcomes, we note the possible advantage of incorporating the gracilis flap even when it is thought that the Singapore flap is sufficient. However, more data are needed.

Treatment of Non-melanoma Skin Cancers in the Absence of Mohs Micrographic Surgery.

Non-melanoma skin cancers are the most common malignancies globally. Although non-melanoma skin cancers exhibit low metastatic potential, they can be locally destructive, necessitating complex excisions and reconstructions. Mohs micrographic surgery is the gold-standard treatment for high-risk non-melanoma skin cancers in patients who are appropriate surgical candidates. Despite its efficacy, Mohs micrographic surgery is not readily available in most geographic regions, necessitating that plastic surgeons be well-versed in alternative treatment modalities for non-melanoma skin cancer. Herein, we will discuss the management of non-melanoma skin cancers in settings where Mohs micrographic surgery is not readily available.

Hydrodynamic Interactions, Hidden Order, and Emergent Collective Behavior in an Active Bacterial Suspension.

Spontaneous self-organization (clustering) in magnetically oriented bacteria arises from attractive pairwise hydrodynamics, which are directly determined through experiment and corroborated by a simple analytical model. Lossless compression algorithms are used to identify the onset of many-body self-organization as a function of experimental tuning parameters. Cluster growth is governed by the interplay between hydrodynamic attraction and magnetic dipole repulsion, leading to logarithmic time dependence of the cluster size. The dynamics of these complex, far-from-equilibrium structures are relevant to broader phenomena in condensed matter, statistical mechanics, and biology.

Tuning bacterial hydrodynamics with magnetic fields.

Magnetotactic bacteria are a group of motile prokaryotes that synthesize chains of lipid-bound, magnetic nanoparticles called magnetosomes. This study exploits their innate magnetism to investigate previously unexplored facets of bacterial hydrodynamics at surfaces. Through use of weak, uniform, external magnetic fields and local, micromagnetic surface patterns, the relative strength of hydrodynamic, magnetic, and flagellar force components is tuned through magnetic control of the bacteria's orientation. The resulting swimming behaviors provide a means to experimentally determine hydrodynamic parameters and offer a high degree of control over large numbers of living microscopic entities. The implications of this controlled motion for studies of bacterial motility near surfaces and for micro- and nanotechnology are discussed.

The failing Fontan: what's NEXT...?

The Fontan procedure represents the final stage of the transition to single ventricle physiology. Conversion of very complex congenital heart anatomy, such as hypoplastic left heart syndrome, double-outlet right ventricle or double-inlet left ventricle, to a single ventricle has grown in popularity as morbidity and mortality have improved. As these patients grow, survivors are at risk for impaired ventricular dysfunction, plastic bronchitis, protein-losing enteropathy and late failure. Late failing Fontan patients represent a particularly vexing scenario for clinicians, as the only durable treatment option is cardiac transplantation. However, in the short-term, some of these patients require support beyond medical management, with mechanical circulatory support via extracorporeal life support or a ventricular assist device. We report the successful bridge of an adolescent female post-Fontan conversion with late severe cardiac failure. The patient was initially resuscitated with extracorporeal life support, transitioned to a single Berlin Heart EXCOR® ventricular assist device and, subsequently, underwent successful cardiac transplantation.

Total artificial heart in the pediatric patient with biventricular heart failure.

Mechanical circulatory support emerged for the pediatric population in the late 1980s as a bridge to cardiac transplantation. The Total Artificial Heart (TAH-t) (SynCardia Systems Inc., Tuscon, AZ) has been approved for compassionate use by the Food and Drug Administration for patients with end-stage biventricular heart failure as a bridge to heart transplantation since 1985 and has had FDA approval since 2004. However, of the 1,061 patients placed on the TAH-t, only 21 (2%) were under the age 18. SynCardia Systems, Inc. recommends a minimum patient body surface area (BSA) of 1.7 m(2), thus, limiting pediatric application of this device. This unique case report shares this pediatric institution's first experience with the TAH-t. A 14-year-old male was admitted with dilated cardiomyopathy and severe biventricular heart failure. The patient rapidly decompensated, requiring extracorporeal life support. An echocardiogram revealed severe biventricular dysfunction and diffuse clot formation in the left ventricle and outflow tract. The decision was made to transition to biventricular assist device. The biventricular failure and clot formation helped guide the team to the TAH-t, in spite of a BSA (1.5 m(2)) below the recommendation of 1.7 m(2). A computed tomography (CT) scan of the thorax, in conjunction with a novel three-dimensional (3D) modeling system and team, assisted in determining appropriate fit. Chest CT and 3D modeling following implantation were utilized to determine all major vascular structures were unobstructed and the bronchi were open. The virtual 3D model confirmed appropriate device fit with no evidence of compression to the left pulmonary veins. The postoperative course was complicated by a left lung opacification. The left lung anomalies proved to be atelectasis and improved with aggressive recruitment maneuvers. The patient was supported for 11 days prior to transplantation. Chest CT and 3D modeling were crucial in assessing whether the device would fit, as well as postoperative complications in this smaller pediatric patient.

Use of an electrothermal bipolar sealing device in ligation of major mesenteric vessels during laparoscopic colorectal resection.

BACKGROUND: A variety of approaches are available for division of major vascular structures during laparoscopic colorectal resection. Ultrasonic coagulating shears (UCS), vascular staplers, plastic or titanium clips and electrothermal bipolar vessel sealing (EBVS) are currently available. We report our experience with an EBVS device, LigaSure™ (Covidien AG), used in division of the ileocolic, middle colic and inferior mesenteric arteries during laparoscopic colorectal resection. METHODS: We report the immediate outcome of 802 consecutive unselected patients who underwent elective laparoscopic colorectal cancer resection performed with use of the LigaSure™ (5 and 10 mm) at our institution over a 5-year period. Operative procedures included right hemicolectomy (n = 180), left hemicolectomy (n = 96), sigmoid colectomy (n = 347) and anterior resection (n = 179). Data were collected from a prospectively maintained cancer database and operative records. The procedures were performed primarily by three consultant surgeons with an interest in laparoscopic colorectal resection. RESULTS: Of 802 cases in which the LigaSure™ device was employed to divide major vascular structures, immediate effective vessel sealing was achieved in 99.8% (n = 800). Two patients experienced related adverse events both following division of the inferior mesenteric artery with a 5 mm LigaSure™. Both patients had immediate uncontrolled haemorrhage that required laparotomy. CONCLUSIONS: Use of the LigaSure™ device to seal and divide the major mesenteric vessels during laparoscopic colorectal resection is very effective, with a high success rate of 99.8%. Caution should be exercised in elderly atherosclerotic patients, particularly when using the 5-mm LigaSure™ device.

Haematoma in a hydrocele of the canal of Nuck mimicking a Richter's hernia.

We report a haematoma in a hydrocele of the canal of Nuck in a 69-year-old female. She presented with a right-sided groin swelling, the differential for which included an irreducible inguinal hernia or haematoma given her aspirin and clopidegrel use. Successful treatment involved evacuation of the haematoma with excision of the sac. Despite a high index of suspicion for a haematoma, these swellings should ideally be explored given the potential for co-existence of a hernia.

Inhibition of N-ethylmaleimide-sensitive factor protects against myocardial ischemia/reperfusion injury.

Exocytosis of endothelial granules promotes thrombosis and inflammation and may contribute to the pathophysiology of early reperfusion injury following myocardial ischemia. TAT-NSF700 is a novel peptide that reduces endothelial exocytosis by inhibiting the ATPase activity and disassembly activity of N-ethylmaleimide-sensitive factor (NSF), a critical component of the exocytic machinery. We hypothesized that TAT-NSF700 would limit myocardial injury in an in vivo murine model of myocardial ischemia/reperfusion injury. Mice were subjected to 30 minutes of ischemia followed by 24 hours of reperfusion. TAT-NSF700 or the scrambled control peptide TAT-NSF700scr was administered intravenously 20 minutes before the onset of ischemia. Myocardial ischemia/reperfusion caused endothelial exocytosis, myocardial infarction, and left ventricular dysfunction. However, TAT-NSF700 decreased von Willebrand factor levels after myocardial ischemia/reperfusion, attenuated myocardial infarct size by 47%, and preserved left ventricular structure and function. These data suggest that drugs targeting endothelial exocytosis may be useful in the treatment of myocardial injury following ischemia/reperfusion.